We examined the phagocytic activity of PMN from patients recovering from infection, using sheep erythrocytes opsonized with purified complement components and IgG as target cells. By controlling the input of IgG, the contribution of complement to phagocytic uptake could be assessed. By treating PMN with sodium azide, we were able to increase phagocytosis by several fold. We found that PMN FROM patients with chronic granulomatous disease (CGD) were similar to PMN of healthy controls in their ability to phagocytose particles coated with C3b and limiting inputs of IgG. Howver, when higher concentrations of IgG were used to sensitize cells and C3b was not present, CGD PMN were markedly more phagocytic than PMN from normal controls. This suggests that CGD, Fc receptor function is upregulated. PMN from other patients who were recovering from a variety of infections, were shown to have enhanced expression of C3b receptors. Our data suggests that there is enhanced ingestion of particles coated with C3b plus limited amounts of IgG in infected patients. Also particles bearing C1q, plus IgG showed enhanced ingestion in these patients, whereas strictly Fc mediated ingestion was similar to normal controls. Thus, infected patients show enhanced phagocytosis depending on how the target cells are opsonized. Unlike the control patients, the enhanced activity in CGD appears to be mediated by the Fc receptor. Our laboratory published that adhered monocytes bind particles coated with the C3b degradation fragment, C3d, under certain conditions of activation or differentiation. Now we have examined the complement receptor responsible for C3d binding and its physiologic function. We showed that C3d, like the fragments iC3b and iC3b, enhances IgG mediated phagocytosis by monocytes. It appears that C3d binds to monocytes via the C3b and iC3b receptors which are apparently altered during the adherence process. These findings show for the first time that the C3d fragment has an opsonic function.